The blood parasite Babesia microti and the spirochetal agent of Lyme disease, B. burgdorferi, are both transmitted by the deer tick, Ixodes dammini ( also called I. scapularis) and are transmitted in areas that are currently endemic for Lyme disease. In humans, infection with these two organisms may occur alone or in combination, and initial prospective studies suggest that persistence of infection with B. burgdorferi and the B. microti piroplasm may be enhanced by concurrent infection. Cryptic Babesia microti infection is of special concern to blood banks in endemic areas, since asymptomatic blood donors harboring infection with the protozoan have been implicated in many transfusion-acquired cases in this country, and one transfusion-acquired case has now occurred with the newly described Babesia-like piroplasm (WAI) in the western United States. Surprisingly little is known about the natural history of babesial infection. The specific aims enumerated here are oriented toward defining further the course of babesiosis in humans and in mouse models of acute and chronic infection that we are studying. First, since most piroplasm species studied to date comprise a chronic carrier state as part of their transmission cycle, we will attempt to document the chronic carrier state in humans, and to monitor the course of infection by using molecular and immunologic methods. Second, we animals and humans by constructing genetic expression libraries from piroplasm-specific genomic DNA, followed by immunologic screening of the libraries with reactive sera. This will help us to identify babesial proteins that are expressed in vivo and will define with greater precision the serologic responses during piroplasm infection. In the third aim, we will develop and evaluate mouse models of infection with a special emphasis on mouse strain susceptibility to piroplasm infection. Finally, in the fourth aim, we will evaluate the potential immunosuppressive properties of babesial infection in a mouse model of B. burgdorferi and B. microti coinfection. The information gained by these studies will lead ultimately to a better understanding of the natural history of babesial infection and the risks posed to humans infected with this emerging pathogen.